Assessment of hESC-IMRC-Exo for Cardiac and Cerebral Injuries Post-Cardiac Arrest Resuscitation: Safety, Pharmacokinetics, and Efficacy.

Authors

Huijuan Yang, Xiaodan Zhang, Wenbin Zhang, Xue Wang, Jie Wang, Ziwei Chen, Jinyu Zhu, Yufeng Hu, Lu He, Licai Liang, Jiefeng Xu, Mao Zhang

Published in

Journal of cellular and molecular medicine. Volume 30. Issue 12. Pages e71264.

Abstract

Cardiac arrest (CA) is a leading cause of death globally. Exosomes derived from mesenchymal stem cells exhibit favourable production, storage, and safety characteristics, making them a promising alternative for post-CA resuscitation. We assessed the safety, biodistribution, and protective effects of human embryonic stem cell-derived immunity-and-matrix regulatory cells (hESC-IMRC-Exo) for post-CA resuscitation cardiac/cerebral injuries, and preliminarily explored its underlying molecular mechanism. The biotoxicity of IMRC-Exo was evaluated in AC16 and HT22 cells and in mice; its biodistribution was traced using fluorescently labelled IMRC-Exo. Protective effects were examined in H/R-treated cells and rat and swine CA models. We found that IMRC-Exo did not induce apoptosis or oxidative stress in AC16 or HT22 cells. IMRC-Exo was also safe in mice, with normal body weight, blood indices, and histopathology. Pharmacokinetic analysis revealed rapid multi-organ distribution, peaking at 24 h with a 7-day half-life. For efficacy study, IMRC-Exo reduced LDH release, ROS levels, and apoptosis in H/R-treated cells. In rat, IMRC-Exo dose-dependently (0.5×, 1×, 2×) reduced serum biomarkers, improved neurological function, and attenuated inflammation. In swine, single-dose IMRC-Exo (1×) reduced injury biomarkers, improved neurological function, and attenuated inflammation. Furthermore, in a separate rat group, IMRC-Exo improved 7-day survival and neurological function. Mechanistically, the protective effects of IMRC-Exo were mediated by its secreted miR-21-5p, which attenuated H/R-induced apoptosis and inflammation by targeting PDCD4. This study demonstrated IMRC-Exo, a safe and effective therapeutic, distributed rapidly via the bloodstream to target organs and protected against post-resuscitation cardiac/cerebral injuries, potentially through the miR-21-5p/PDCD4 axis.

PMID:
42363421
Bibliographic data and abstract were imported from PubMed on 27 Jun 2026.

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